Regulation of plasma long-chain fatty acid oxidation in relation to uptake in human skeletal muscle during exercise
Abstract
In the present study, we investigated possible sites of regulation of long-chain fatty acid (LCFA) oxidation in contracting human skeletal muscle. Leg plasma LCFA kinetics were determined in eight healthy men during bicycling (60 min, 65% peak oxygen uptake) with either high (H-FOX) or low (L-FOX) leg fat oxidation (H-FOX: 1,098 ± 140; L-FOX: 494 ± 84 μmol FA/min, P < 0.001), which was achieved by manipulating preexercise muscle glycogen (H-FOX: 197 ± 21; L-FOX: 504 ± 25 mmol/kg dry wt, P < 0.001). Several blood metabolites and hormones were kept nearly similar between trials by allocating a preexercise meal and infusing glucose intravenously during exercise. During exercise, leg plasma LCFA fractional extraction was identical between trials (H-FOX: 17.8 ± 1.6; L-FOX: 18.2 ± 1.8%, not significant), suggesting similar LCFA transport capacity in muscle. On the contrary, leg plasma LCFA oxidation was 99% higher in H-FOX than in L-FOX (421 ± 47 vs. 212 ± 37 μmol/min, P < 0.001). Probably due to the slightly higher ( P < 0.01) plasma LCFA concentration in H-FOX than in L-FOX, leg plasma LCFA uptake was nonsignificantly ( P = 0.17) higher (25%) in H-FOX than in L-FOX, yet the fraction of plasma LCFA uptake oxidized was 61% higher ( P < 0.05) in H-FOX than in L-FOX. Accordingly, the muscle content of several lipid-binding proteins did not differ significantly between trials, although fatty acid translocase/CD36 and caveolin-1 were elevated ( P < 0.05) by the high-intensity exercise and dietary manipulation allocated on the day before the experimental trial. The present data suggest that, in contracting human skeletal muscle with different fat oxidation rates achieved by manipulating preexercise glycogen content, transsarcolemmal transport is not limiting plasma LCFA oxidation. Rather, the latter seems to be limited by intracellular regulatory mechanisms.
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When fat oxidation is decreased and CD36 levels are increased, muscle uptake of long-chain fatty acids increases, resulting in increased muscle triglyceride synthesis and increased intramyocellular lipid content.
“During conditions of decreased fat oxidation and increased CD36 levels, muscle uptake of LCFA increased, resulting in increased muscle triglyceride synthesis and increased IMCL content [97, 98].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [98]
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- Authors
- Roepstorff, C., Vistisen, B., Roepstorff, K., & Kiens, B.
- Affiliations
- Copenhagen Muscle Research Centre (DK)
- ORCID
- Kiens, Bente
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2004-10
- Volume
- 287
- Issue
- 4
- Pages
- E696-E705
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2119950488
- Cited by
- 40
- References
- 52
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 2 · 2012: 2
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- long-chain fatty acid oxidation, skeletal muscle, physical activity, muscle glycogen, fatty acid uptake, CD36, caveolin-1, high-intensity exercise
- MeSH terms
- Adult, Carrier Proteins, Diet, Eating, Fatty Acids, Glucose, Glycogen, Humans, Infusions, Intravenous, Leg, Male, Muscle Contraction, Oxidation-Reduction, Sarcolemma, Blotting, Western, Exercise, Respiratory Mechanics, Muscle, Skeletal, CD36 Antigens, Caveolins, Organic Anion Transporters, Fatty Acid-Binding Proteins, Caveolin 1, Caveolin 3
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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